Objectives: To study whether the addition of metformin further improves the blood lipid pattern in non-diabetic patients with coronary heart disease already treated with lovastatin, diet and lifestyle advice.
Design: An open, prospective, randomized study in a university hospital setting.
Subjects: Sixty non-diabetic male patients previously treated with coronary artery bypass surgery or angioplasty and with serum cholesterol > or = 6.0 mmol L-1 and/or HDL-cholesterol < or = 1.2 mmol L-1.
Interventions: After a 4-week run-in period with lovastatin (40 mg day-1), and diet and lifestyle advice, patients were randomized into two groups, both continuing the run in treatment. One group received metformin up to 2000 mg day-1; the control group got no additional treatment.
Main outcome measures: Fasting serum lipids, glucose and weight were registered at entrance (= week-4), and at weeks 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were compared. Side-effects of the treatment were also registered.
Results: Metformin lowered the LDL/HDL-cholesterol ratio by 12 and 6% at weeks 4 and 12, respectively, and reduced body weight by 1.8 kg at week 12. There was also a transient lowering effect on LDL-cholesterol and apolipoprotein B. In the normal weight subgroup of patients (body mass index < 27 kg m-2), metformin induced a decrease in total cholesterol (-9%). LDL-cholesterol (-12%). LDL/HDL-cholesterol ratio (-10%) and apolipoprotein B (-7%), as compared to the control group. In this subgroup, body weight and fasting glucose were unaffected by metformin. Thus, the lipid lowering effect in normal weight patients was not secondary to changes in body weight or fasting glucose. In overweight patients (body mass index > 27 kg m-2), metformin had no significant effects on blood lipids, but induced a weight loss of -3.0 kg and a transient reduction of fasting glucose. No side-effects were registered apart from those expected from each individual drug.
Conclusions: Metformin given for 12 weeks as a supplement to lovastatin, diet and lifestyle advice to non-diabetic male patients with coronary heart disease further improves the lipid pattern in normal weight patients, and reduces weight in the overweight patients. Because metformin is cheap and other lipid lowering drugs are expensive, the potential of metformin as a lipid lowering agent should be further investigated.